High-Throughput Cellular Heterogeneity Analysis in Cell Migration at the Single-Cell Level
Mengli Zhou
UPMC Hillman Cancer Center, University of Pittsburgh, 5115 Centre Ave, Pittsburgh, PA, 15232 USA
Department of Computational and Systems Biology, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA, 15260 USA
Xiangya Hospital, Central South University, Changsha, Hunan, 410008 China
Search for more papers by this authorYushu Ma
UPMC Hillman Cancer Center, University of Pittsburgh, 5115 Centre Ave, Pittsburgh, PA, 15232 USA
Department of Computational and Systems Biology, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA, 15260 USA
Search for more papers by this authorChun-Cheng Chiang
UPMC Hillman Cancer Center, University of Pittsburgh, 5115 Centre Ave, Pittsburgh, PA, 15232 USA
Department of Computational and Systems Biology, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA, 15260 USA
Search for more papers by this authorEdwin C. Rock
Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA, 15260 USA
Search for more papers by this authorKathryn E. Luker
Center for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200 USA
Search for more papers by this authorGary D. Luker
Department of Microbiology and Immunology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200 USA
Center for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200 USA
Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel, Blvd, Ann Arbor, MI, 48109-2099 USA
Search for more papers by this authorCorresponding Author
Yu-Chih Chen
UPMC Hillman Cancer Center, University of Pittsburgh, 5115 Centre Ave, Pittsburgh, PA, 15232 USA
Department of Computational and Systems Biology, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA, 15260 USA
Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA, 15260 USA
CMU-Pitt Ph.D. Program in Computational Biology, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA, 15260 USA
E-mail: [email protected]
Search for more papers by this authorMengli Zhou
UPMC Hillman Cancer Center, University of Pittsburgh, 5115 Centre Ave, Pittsburgh, PA, 15232 USA
Department of Computational and Systems Biology, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA, 15260 USA
Xiangya Hospital, Central South University, Changsha, Hunan, 410008 China
Search for more papers by this authorYushu Ma
UPMC Hillman Cancer Center, University of Pittsburgh, 5115 Centre Ave, Pittsburgh, PA, 15232 USA
Department of Computational and Systems Biology, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA, 15260 USA
Search for more papers by this authorChun-Cheng Chiang
UPMC Hillman Cancer Center, University of Pittsburgh, 5115 Centre Ave, Pittsburgh, PA, 15232 USA
Department of Computational and Systems Biology, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA, 15260 USA
Search for more papers by this authorEdwin C. Rock
Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA, 15260 USA
Search for more papers by this authorKathryn E. Luker
Center for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200 USA
Search for more papers by this authorGary D. Luker
Department of Microbiology and Immunology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200 USA
Center for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200 USA
Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel, Blvd, Ann Arbor, MI, 48109-2099 USA
Search for more papers by this authorCorresponding Author
Yu-Chih Chen
UPMC Hillman Cancer Center, University of Pittsburgh, 5115 Centre Ave, Pittsburgh, PA, 15232 USA
Department of Computational and Systems Biology, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA, 15260 USA
Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA, 15260 USA
CMU-Pitt Ph.D. Program in Computational Biology, University of Pittsburgh, 3420 Forbes Avenue, Pittsburgh, PA, 15260 USA
E-mail: [email protected]
Search for more papers by this authorAbstract
Cancer cell migration represents an essential step toward metastasis and cancer deaths. However, conventional drug discovery focuses on cytotoxic and growth-inhibiting compounds rather than inhibitors of migration. Drug screening assays generally measure the average response of many cells, masking distinct cell populations that drive metastasis and resist treatments. Here, this work presents a high-throughput microfluidic cell migration platform that coordinates robotic liquid handling and computer vision for rapidly quantifying individual cellular motility. Using this innovative technology, 172 compounds were tested and a surprisingly low correlation between migration and growth inhibition was found. Notably, many compounds were found to inhibit migration of most cells while leaving fast-moving subpopulations unaffected. This work further pinpoints synergistic drug combinations, including Bortezomib and Danirixin, to stop fast-moving cells. To explain the observed cell behaviors, single-cell morphological and molecular analysis were performed. These studies establish a novel technology to identify promising migration inhibitors for cancer treatment and relevant applications.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
Supporting Information
| Filename | Description |
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| smll202206754-sup-0001-SuppMat.pdf610.2 KB | Supporting Information |
| smll202206754-sup-0002-VideoS1.mp413.4 MB | Supplemental Video 1 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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